The proposed research concerns the physiology of synaptic transmission in the outer synaptic layer of the vertebrate retina. The large amplification which occurs when signals are transmitted across the first synapses in the visual system and the ability of these synapses to adapt to relatively large changes in presynaptic voltage are not explained by what we know from the study of other synapses. The proposed research will characterize how transmitters are released, the identity of the molecules released, and their postsynaptic effect. The mechanism by which transmitters are released will be studied by impaling solitary photoreceptors with micro pipettes and measuring the voltage and time dependence of the presynaptic calcium current. Transmitters will be identified by culturing isolated photoreceptors in media supplemented with radioactive precursor molecules, collecting the radioactive molecules released when the cells are stimulated, and analyzing these molecules with biochemical methods including high pressure liquid chromatography. The post synaptic effect of the identified transmitters will be determined by measuring the electrical response when known compounds are iontophoresed onto solitary horizontal cells. The purpose of these experiments is to provide information on the mechanism of synaptic transmission and to obtain a clearer understanding of the normal working of the vertebrate retina.